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  • Title: Inhibition of rat endotoxin-induced lethality by BN 52021 and BN 52063, compounds with PAF-acether antagonistic effect and protease-inhibitory activity.
    Author: Etienne A, Hecquet F, Guilmard C, Soulard C, Braquet P.
    Journal: Int J Tissue React; 1987; 9(1):19-26. PubMed ID: 3596954.
    Abstract:
    Since proteolytic enzymes play a key role in endotoxaemia and anaphylaxis, diseases in which PAF-acether may be involved, we have investigated the activity of BN 52021 and BN 52063, two potent and specific PAF-acether antagonists, on plasma protease activity in the rat. After oral administration, both drugs dose-dependently decreased plasma trypsin-like activity (PTLA) although they did not show any inhibitory effect in vitro. PAF-acether and endotoxin injected into rats increased PTLA, the increase with endotoxin appearing more slowly but to a higher extent than with PAF-acether. Inhibition of the endotoxin-induced increase in PTLA was obtained with BN 52021, BN 52063 and dexamethasone, whereas aprotinin was ineffective. Since BN 52021 and BN 52063 reduced also the endotoxin-induced lethality in the rat, their antiprotease activity may be a consequence of their PAF-antagonistic effect. Further studies will be required with other PAF antagonists to assess fully this assumption.
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